POS1227 TIME BETWEEN SECOND AND THIRD DOSES INFLUENCES RESPONSE TO COVID-19 VACCINE IN AUTO-IMMUNE DISEASE PATIENTS TREATED WITH RITUXIMAB WITHOUT RESPONSE TO TWO DOSES.
Authors: S. Bitoun, J. Avouac, J. Henry, R. Ghossan, O. Al Tabaa, R. Belkhir, G. Nocturne, C. Vauloup-Fellous, X. Mariette, R. Seror
Journal: Annals of the Rheumatic Diseases (2022)

Background It is now well established that patients treated with rituximab (RTX) for auto-immune disease (AID) have a diminished antibody response to COVID-19 vaccines after two doses. Optimizing antibody response is a key objective in this population. To achieve this goal, a 3 rd booster dose may be considered. Objectives Focusing on the population of AID patients treated with RTX without any antibody response after two doses we sought to explore how these patients could respond to a 3 rd dose and identify factors of response. Methods We performed a French retrospective bicentric observational trial which is a follow up of previously published work (1). We included consecutive patients treated with RTX that were non-responders regarding their anti-Spike antibody (anti-S) status at least one month after the second dose of COVID-19 vaccination. Patients were included between March and October 2021. All patients then received a third dose according to local guidelines and had an anti-S measurement at least one month after the third dose. Some patients without response to a third dose had a fourth dose. Anti-S were measured in serum with various kits, but all results were in BAU/mL with upper quantification limit at 243. Patients with anti-S above 49 BAU/mL, which has been demonstrated to be the threshold associated with detectable neutralizing response were considered as responders (1). Results 60 patients treated with RTX without response to 2 doses (Anti-S Ab &lt; 49 BAU/mL) were included in the study. 9/60 (15%) patients responded to the 3 rd vaccine dose with anti-S &gt; 49BAU/ml. Responders and non-responders had similar demographic characteristics (Table 1). There was a positive correlation between anti-S Ab levels after dose 3 and time between 2 nd and 3 rd doses (r=0,41 p=0,001) (Figure 1). Nevertheless, the median time between 2 nd and 3 rd doses was numerically but not significantly higher in responders than in non-responders (129 vs 80 days, p=0.30). There was no correlation between anti-S levels after the third dose and the time between the last RTX infusion and the third vaccine dose. There was a trend towards more patients with methotrexate co-medication in the non-responder group 31/51 (61%) vs 3/9 (33%) in the responder group (p=0,15). Seven non-responder patients after the 3 rd dose received a 4 th dose and 4 (57%) responded. Table 1. Characteristics of patients without response after the second dose of vaccine treated with Rituximab for auto-immune diseases according to their seroconversion status after the third dose. Non responders (n=51 ) Responders (n=9 ) p Age, median (min-max) 61 (17-85) 58 (36-78) 0,33 Female sex n (%) 42 (82) 6 (67) 0,36 Underlying disease n (%) Rheumatoid Arthritis 36 (69) 5 (56) 0,46 Other auto-immune disease 16 (31) 4 (44) Rituximab treatment Received a RTX infusion between dose 2 and 3 n (%) 14(27) 3(33) 0,70 Time between the last RTX infusion and the 3 rd dose of vaccine in days median (min-max) 162 (1-687) 187 (79-959) 0,16 Previous number of RTX injections, median (min-max) 7 (0-34) 6 (1-22) 0,58 Vaccination scheme Interval between 2 nd and 3 rd vaccine dose in days, median (min-max) 80 (23-287) 129 (24-220) 0,30 Less than 3 months between 2 nd and 3 rd vaccine dose n (%) 27(53) 2(22) 0,14 Co-medications Patients on steroids n (%) 20(40) 5 (37,5) 0,99 Prednisone equivalent dose per day in mg median (min-max) 5(2-25) 5(5-10) 0,48 Figure 1. Correlation between anti- spike Ab levels after the third dose and time in days between doses 2 and 3. Conclusion A third vaccine dose of COVID-19 vaccine leads to only 15% of response in previously non-responding RTX treated AID patients. A longer time between 2 nd and 3 rd doses might positively influences response to a 3 rd COVID-19 vaccine. Finally exploratory findings show that a fourth dose could be useful to obtain response non-responders. References [1]Bitoun S, Henry J, Desjardins D, et al. Rituximab impairs B-cell response but not T-cell response to COVID-19 vaccine in auto-immune diseases. Arthritis Rheumatol Hoboken NJ Published Online First: 28 December 2021. Disclosure of Interests None declared